In multiple sclerosis patients a single serum neurofilament light chain (sNFL) dosage is strongly associated with 12 months outcome: data from a real-life clinical setting.

Background: Neurofilament light chain (NFL) is a neuroaxonal cytoskeletal protein released into cerebrospinal fluid (CSF) and eventually into blood upon neuronal injury. Its detection in serum (sNFL) makes it a promising marker in multiple sclerosis (MS).

Objective: To evaluate the usefulness of a single dosage of sNFL in clinical practice.

Methods: 626 consecutive relapsing-remitting (RR) MS patients treated with disease modifying treatments (DMTs) for at least 12 months underwent a single sNFL dosage. 553 patients had NEDA-3 status (no relapses, no disability progression, no new/enlarging or contrast-enhancing lesions on brain magnetic resonance imaging) in the 12 months prior blood sampling. sNFL levels were measured by single molecule array (Simoa™). Association between sNFL levels and NEDA-3 status at 12, 24, and 36 months was evaluated with logistic regression models adjusted for sex, EDSS, disease duration, and type of DMTs.

Results: 469 out of the 553 NEDA-3 patients had normal sNFL level, whereas 42 had elevated level. The two groups did not differ regarding baseline characteristics. A very strong association between elevated sNFL levels and loss of NEDA-3 status within 12 months was found, with an odds ratio [OR] of 10.74 (95% CI 4.34-26.57); 15 and 10 patients with normal and elevated sNFL, respectively lost NEDA-3 (p < 0.001). The effect was not detected during the subsequent 13-24 and 25-36 months.

Conclusions: A single elevated sNFL is strongly associated with NEDA-3 loss within 1 year. Elevated sNFL in apparently stable patients suggests an ongoing disease activity below the detection threshold of standard parameters.